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中国临床药理学与治疗学 ›› 2025, Vol. 30 ›› Issue (4): 464-476.doi: 10.12092/j.issn.1009-2501.2025.04.004

• 基础研究 • 上一篇    下一篇

基于网络药理学探讨白连降浊方治疗脂质异常的机理

刘艮1,2,杨卫东1,李佳2,刘聪2,郝旭亮3   

  1. 1山西中医药大学,晋中030619,山西;2山西省中医药研究院,太原 030012,山西;3山西中医药大学附属医院,太原030024,山西

  • 收稿日期:2023-12-14 修回日期:2024-03-20 出版日期:2025-04-26 发布日期:2025-04-09
  • 通讯作者: 郝旭亮,男,博士,教授,主任药师,硕士生导师,研究方向:中药药效物质基础及作用机制研究、中药新药及健康产品开发研究。 E-mail: hxliang-01@163.com
  • 作者简介:刘艮,女,在读硕士研究生,研究方向:中药制剂与质量控制分析研究。 E-mail: 2123982787@qq.com
  • 基金资助:
    2022年山西省重点研发计划项目(202202130501012);山西省技术创新中心项目(202104010911024)

Exploring the mechanism of action of BLJZF in the treatment of lipid abnormalities

LIU Gen1,2, YANG Weidong1, LI Jia2, LIU Cong2, HAO Xuliang3   

  1. 1Shanxi University of Chinese Medicine, Jinzhong 030619, Shanxi, China; 2Shanxi Academy of Traditional Chinese Medicine, Taiyuan 030012, Shanxi, China; 3Affiliated Hospital of Shanxi University of Traditional Chinese Medicine, Taiyuan 030024, Shanxi, China
  • Received:2023-12-14 Revised:2024-03-20 Online:2025-04-26 Published:2025-04-09

摘要:

目的:基于网络药理学、分子对接及体内动物实验,探究白连降浊方(BLJZF)治疗脂质代谢异常的作用机理。方法:试验通过TCMSP数据库、Swiss Target Prediction数据库、STITCH数据库以及文献检索收集并查询BLJZF的组分化学成分信息以及收集药物化学成分对应的作用靶点;通过GeneCards数据库和OMIM数据库收集脂质异常疾病靶点;利用Metascape数据库对共有交集靶点进行基因本体(GO)功能及京都基因与基因组百科全书(KEGG)通路富集分析;利用Cytoscape软件构建成分与靶点等相关网络图,以筛选主要成分与靶点进行分子对接研究。采用高脂饲料饲养诱导高血脂模型,设置空白组、模型组、阳性组、BLJZF组,连续给药4周,检测血清中血脂指标含量:甘油三酯(TG)、总胆固醇(TC)、低脂蛋白胆固醇(LDL-C)和高脂蛋白胆固醇(HDL-C);检测氧化应激指标含量:丙氨酸氨基转移酶(ALT)及天冬氨酸氨基转移酶(AST);用ELISA检测超氧化物歧化酶(SOD)和丙二醛(MDA)的含量;苏木素-伊红(HE)染色检测肝组织病理变化。结果:共整理得到BLJZF的25个成分及相对应的315个靶点,脂质异常靶点1 729个,二者共同靶点116个,其中核心靶点有AKT1、TNF、IL1β、CASP3等。GO和KEGG富集分析提示BLJZF可能通过脂质与动脉粥样硬化途径、PI3K-Akt、糖尿病并发症中的AGE-RAGE等信号通路发挥作用。分子对接显示,大部分核心靶点与活性成分有较高的结合活性。动物实验表明,与模型组相比,BLJZF组TC、TG、LDL-C、ALT、AST、MDA显著降低,HDL-C、SOD显著升高,肝脏脂肪变形程度减轻。结论:BLJZF对脂质异常具有治疗作用,通过多成分、多靶点、多途径治疗脂质代谢异常,为后续BLJZF的药物研究提供参考。

关键词: 脂质异常, 网络药理学, 分子对接, 实验验证, 白莲降浊方

Abstract:

AIM:To explore the mechanism of BLJZF in the treatment of abnormal lipid metabolism based on network pharmacology, molecular docking and in vivo animal experiments. METHODS:TCMSP database, Swiss Target Prediction database, STITCH database and literature search were used to collect and query the chemical composition information of BLJZF and the corresponding target of drug chemical composition. Disease targets of lipid abnormalities were collected through GeneCards and OMIM databases. Metascape database was used to analyze the gene ontology function and the Kyoto Encyclopedia gene and genome pathway enrichment of common intersection targets. Cytoscape software was used to construct the correlation network diagram of components and targets, so as to select major components and targets for molecular docking study. The hyperlipidemia model was induced by high fat diet, and the control group, model group, positive group and BLJZF group were set up. The serum lipid index contents of triglyceride (TG), total cholesterol (TC), low lipoprotein cholesterol (LDL-C) and high lipoprotein cholesterol (HDL-C) were detected after continuous administration for 4 weeks. The contents of oxidative stress index were detected: alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The contents of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by ELISA. Hematoxylin-eosin (HE) staining was used to detect the pathological changes of liver tissue. RESULTS:A total of 25 components and 315 corresponding targets of BLJZF were obtained, 1729 targets of lipid abnormalities and 116 common targets of BLJZF, among which the core targets were AKT1, TNF, IL1β, CASP3, etc. GO and KEGG enrichment analysis suggested that BLJZF may play a role through the lipid and atherosclerotic pathway, PI3K-Akt, AGE-RAGE in diabetic complications and other signaling pathways. Molecular docking showed that most of the core targets had high binding activity with the active ingredients. Animal experiments showed that compared with model group, TC, TG, LDL-C, ALT, AST and MDA in BLJZF group were significantly decreased, HDL-C and SOD were significantly increased, and the degree of liver fat deformation was reduced.CONCLUSION: BLJZF has a therapeutic effect on lipid abnormalities. It can treat lipid metabolism abnormalities through multi-component, multi-target and multi-pathway, and provide reference for subsequent drug research on BLJZF.

Key words: lipid abnormalities, network pharmacology, molecular docking, experimental verification, BLJZF

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